High number of CD14+B7H4+ monocytes is significantly associated with increased concentrations of IL-4, IL-13, IL-10, and TGF-β1 in tumor microcirculation of lung carcinoma

Jelena Vuković; Nevena Nikolić; Vukoica Karličić; Ivan Stanojević; Gordana Šupić; Milena Jović; Debora Štefik; Džihan Abazović; Danilo Vojvodić

doi:10.2298/VSP200229043V

Jelena Vuković Military Medical Academy, Clinic for Lung Disease, Belgrade, Serbia
Nevena Nikolić University of Defence, Faculty of Medicine of the Military Medical Academy, Belgrade, Serbia
Vukoica Karličić Military Medical Academy, Clinic for Lung Disease, Belgrade, Serbia
Ivan Stanojević University of Defence, Faculty of Medicine of the Military Medical Academy, Belgrade, Serbia
Gordana Šupić University of Defence, Faculty of Medicine of the Military Medical Academy, Belgrade, Serbia
Milena Jović Military Medical Academy, Institute for Pathology, Belgrade, Serbia
Debora Štefik Renova Center for Regenerative Medicine, Belgrade, Serbia
Džihan Abazović Renova Center for Regenerative Medicine, Belgrade, Serbia
Danilo Vojvodić University of Defence, Faculty of Medicine of the Military Medical Academy, Belgrade, Serbia

DOI: https://doi.org/10.2298/VSP200229043V

Keywords: antigens, cd, blood, cytokines, histological techniques, lung neoplasms, monocytes

Abstract

Background/Aim. Lung cancer (LC) is one of the leading causes of mortality. Disease progression and advanced disease are characterized by the unprotective immune response due to M2 macrophage polarization, myeloid-derived suppressor cells (MDSC) activity, cytokine imbalance, and regulatory T lymphocyte activity. The aim of this study was to investigate the association between Th₁/Th₂ cytokines and CD14⁺B7H4⁺ monocyte (Mo) number in LC patients. Methods. We investigated principal Th₁/Th₂cytokines and CD14⁺B7H4⁺ Mo number in blood and tumor microcirculation samples of 41 LC patients (III and IV clinical stage) and 30 healthy participants (control group). Results. The serum concentrations of investigated cytokines in all patients vs. heathy controls did not differ significantly. Stratification in groups according to tumor histology, disease extent, and tumor size revealed significant differences. LC patients with different histology types demonstrated significant differences, both in serum and tumor microcirculation samples. The presence of metastasis was associated with increased IFN-γ/IL-4 in blood and increased IL-13 in tumor microcirculation samples. Tumor microcirculation samples of the largest tumors were characterized by the Th₂ cytokine profile. Investigation of CD14⁺B7H4⁺ Mo in blood samples demonstrated a significant association of extreme value of this cell population with elevated IL-2/IL-13. Patients with the highest CD14⁺B7H4⁺ Mo number in tumor microcirculation samples demonstrated significant increments of IL-4, IL-13, IL-10, and TGF-b₁. Conclusion. LC patients demonstrated polarization of cytokine response associated with microenvironment origin, tumor histology type, tumor size, and disease extent. The highest number of CD14⁺ B7H4⁺ monocytes is significantly associated with the Th₂cytokine profile.

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